BigWigs

There has been a notable increase in interest in the transcriptional regulator Kaiso, which has been linked to the regulation of clonal haematopoiesis, myelodysplastic syndromes, and tumourigenesis. Nevertheless, there is as yet no consistent data on the binding sites of Kaiso in vivo in the genome. In this study, we employed Caki-1 kidney carcinoma cells and their derivative, which lacks the Kaiso gene, to ascertain the genomic targets of Kaiso. The principal binding motifs for Kaiso are CGCG and CTGCNAT, with 72% of all binding sites containing both sequences. The significance of methyl-DNA binding activity was confirmed through the examination of the genomic distribution of the E535A mutant variant of Kaiso, which cannot bind methylated DNA in vitro but remains competent to interact with CTGCNA sequences. Our findings indicate that Kaiso is present at CpG islands with a preference for methylated CpG islands. Furthermore, Kaiso binding sites exhibit enrichment at CpG islands with partial methylation at the 5' and/or 3' boundaries, as well as wave-like methylation patterns. The present study delineates the genomic distribution of Kaiso in cancer cells, thereby confirming its role as a factor with a complex mode of DNA binding and a strong association with CpG islands.